Determination of synergy by two methods with eight antimicrobial combinations against tobramycin-susceptible and tobramycin-resistant strains of pseudomonas

Chan, Edward L.; Zabransky, R.J.

doi:10.1016/0732-8893(87)90101-5

Cited by 38 publications

(33 citation statements)

References 11 publications

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“…Furthermore, for any one method, lack of standardized methodology or interpretative criteria contributes to the broad range of results presented in the literature (Tables 1 and 2 (154). Similarly, comparison of beta-lactam-aminoglycoside interactions against P. aeruginosa by checkerboard MIC testing and 6-or 24-h time-kill curves results in concordance rates of <50% between any pair of methods (35,36). On the other hand, several studies examining small numbers of strains have suggested rough correlations between results obtained by different methods (110,191).…”

Section: Correlation Of Results By Various Methodsmentioning

confidence: 99%

Antibiotic combinations: should they be tested?

1988

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When antibiotic combinations are used to provide a broader spectrum of antimicrobial activity or in an attempt to prevent the emergence of resistant organisms, it is rarely necessary or practical to perform tests of drug interactions in vitro. In vitro testing of combinations may be useful when combinations are used in an attempt to attain synergistic interactions. In some cases, screening methods can be used as substitutes for formal synergy testing. This paper examines the mechanisms of antibiotic interaction leading to synergism or antagonism, surveys attempts to correlate in vitro observations with efficacy in animal models, and reviews clinical data providing evidence for or against a useful role of synergistic antibiotic interactions in the treatment of human infections.

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Section: Correlation Of Results By Various Methodsmentioning

confidence: 99%

Antibiotic combinations: should they be tested?

1988

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“…Furthermore, synergistic activity of aminoglycoside-,-lactam combinations is infrequently observed (3,9). We examined the in vitro susceptibility of 28 clinical isolates of P. maltophilia to ciprofloxacin and three other quinolones (norfloxacin, difloxacin, and A-56620), as well as to nine extended-spectrum 1-lactams (carbenicillin, ticarcillin, piperacillin, imipenem, SCH-34343, aztreonam, ceftazidime, cefoperazone, and cefsulodin) and three aminoglycosides (gentamicin, tobramycin, and amikacin), by an agar dilution method.…”

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confidence: 99%

“…Antagonism was not observed in any combination. These data suggest that combinations of ciprofloxacin with these agents may be useful for some nosocomial multiply drug-resistant P. maltophilia infections.Pseudomonas maltophilia is an important nosocomial pathogen (12) which presents a unique therapeutic challenge because of its tendency to exhibit multiple resistance to aminoglycosides and P-lactams (3,6,9,13). Furthermore, synergistic activity of aminoglycoside-,-lactam combinations is infrequently observed (3, 9).…”

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Synergistic interactions of ciprofloxacin and extended-spectrum beta-lactams or aminoglycosides against multiply drug-resistant Pseudomonas maltophilia

Chow

Wong

Bartlett

1988

Antimicrob Agents Chemother

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The susceptibility of 28 clinical isolates of Pseudomonas maltophilia to 16 antimicrobial agents was determined in vitro by a standard agar dilution method with inoculum sizes of 104 and 106 CFU. All isolates exhibited multiple drug resistance. Nine isolates were selected for studies of combinations of ciprofloxacin with seven antipseudomonal ,-lactams and three aminoglycosides by a checkerboard agar dilution technique. Synergistic or additive combinations of ciprofloxacin in clinically achievable concentrations were most frequent with meziocillin (89%), followed by cefoperazone (67%), piperacillin (56%), cefsulodin (56%), and ceftazidime (33%), and were infrequent with aztreonam (11%), the aminoglycosides (0 to 14%), or imipenem (0%). Antagonism was not observed in any combination. These data suggest that combinations of ciprofloxacin with these agents may be useful for some nosocomial multiply drug-resistant P. maltophilia infections.Pseudomonas maltophilia is an important nosocomial pathogen (12) which presents a unique therapeutic challenge because of its tendency to exhibit multiple resistance to aminoglycosides and P-lactams (3,6,9,13). Furthermore, synergistic activity of aminoglycoside-,-lactam combinations is infrequently observed (3, 9). We examined the in vitro susceptibility of 28 clinical isolates of P. maltophilia to ciprofloxacin and three other quinolones (norfloxacin, difloxacin, and A-56620), as well as to nine extended-spectrum 1-lactams (carbenicillin, ticarcillin, piperacillin, imipenem, SCH-34343, aztreonam, ceftazidime, cefoperazone, and cefsulodin) and three aminoglycosides (gentamicin, tobramycin, and amikacin), by an agar dilution method. Selected strains were used to test for synergy of ciprofloxacin in combination with other agents by a checkerboard agar dilution technique. Demonstration of synergistic activity in vitro with these antimicrobial combinations may suggest useful therapeutic regimens for these difficult infections in the clinical setting.A total of 28 P. maltophilia isolates obtained from patients in Vancouver General Hospital were available for study. Sources included sputum (7 isolates), wounds (7 isolates), urine (2 isolates), cerebro spinal fluid (1 isolate), and miscellaneous sites (11 isolates). In vitro susceptibility to each antibiotic was determined by the agar dilution method (1). A Steers replicator was used to deliver a 0.0025-ml inoculum onto the surface of Mueller-Hinton agar (BBL Microbiology Systems) supplemented with calcium (50 mg/liter) and magnesium (25 mg/liter) and containing twofold serial dilutions of the test antibiotics. Unsupplemented Mueller-Hinton agar contained 1.5 mM calcium and 0.7 mM magnesium, as determined by atomic absorption spectrophotometry. The final cation concentrations in the supplemented medium were 2.7 mM calcium and 1.7 mM magnesium. The effect of inoculum was assessed by testing both inoculum sizes, 104 and 106 CFU per spot, for each organism. Plates without antibiotics served as controls. All plates were incubated for 24 h a...

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“…The checkerboard method, with fractional inhibitory concentration indices and isobolograms, and the killing-curve method are used. Both methods have their advantages and drawbacks (7,8,32,36,37). …”

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confidence: 99%

Fractional Maximal Effect Method for In Vitro Synergy between Amoxicillin and Ceftriaxone and between Vancomycin and Ceftriaxone against Enterococcus faecalis and Penicillin-Resistant Streptococcus pneumoniae

Desbiolles

Piroth

Lequeu

et al. 2001

Antimicrob Agents Chemother

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In the present study we assessed the use of a new in vitro testing method and graphical representation of the results to investigate the potential effectiveness of combinations of amoxicillin (AMZ) plus ceftriaxone (CRO) and of CRO plus vancomycin (VAN) against strains of Streptococcus pneumoniae highly resistant to penicillin and cephalosporins (PRP strains). We used the fractional maximal effect (FME) method of time-kill curves to calculate adequate concentrations of the drugs to be tested rather than relying on arbitrary choices. The concentrations obtained, each of which corresponded to a fraction of the maximal effect, were tested alone and in combination with the bacterial strains in a broth medium. Synergy was defined as a ratio of observed effect/theoretical effect, called FME, of greater than 1, additivity was defined as an FME equal to 1, and antagonism was defined as an observed effect lower than the best effect of one of the antibiotics used alone. The area between antagonism and additivity is the indifference zone. The well-known synergy between amoxicillin and gentamicin against a reference strain of Enterococcus faecalis was confirmed, with a best FME equal to 1.07. Two strains of PRP, strains PRP-1 and PRP-2, were studied. The MICs for PRP-1 and PRP-2 were as follows: penicillin, 4 and 16 g/ml, respectively; AMZ, 2 and 8 g/ml, respectively, CRO, 1 and 4 g/ml, respectively; and VAN, 0.5 and 0.25 g/ml, respectively. For PRP-1 the best FME for the combination AMZ-CRO was 1.22 with drug concentrations of 1.68 mg/liter for AMZ and 0.17 mg/liter for CRO; the best FME for the combination VAN-CRO was 1.75 with VAN at 0.57 mg/liter and CRO at 0.17 mg/liter. For PRP-2 the best FME obtained for the combination AMZ-CRO was 1.05 with drug concentrations of 11.28 mg/liter for AMZ and 0.64 mg/liter for CRO; the best FME obtained for the combination VAN The emergence of strains of Streptococcus pneumoniae highly resistant to penicillin and cephalosporins (PRP strains) (5, 10) and, often, to other classes of antimicrobial agents (33) complicates empirical treatment of pneumococcal infections. Therefore, all potential modalities for the treatment of these infections must be considered (6). Ceftriaxone or vancomycin is often one of the drugs recommended for the treatment of severe infections due to PRP such as meningitis. However, a combination of amoxicillin and ceftriaxone could also be a candidate for the treatment of such infections.In this context, our purpose was, first, to investigate the in vitro interaction between amoxicillin and ceftriaxone and between vancomycin and ceftriaxone against PRP and, second, to identify the range of concentrations that are of clinical interest.The traditional methods used to test the in vitro interactions between drugs are not very satisfactory, with difficulties in the interpretation of the results (16). All these methods come from two original models: the Loewe additivity model (24), illustrated by isobolograms, and the Bliss independence model (4), illustrated by dose-effe...

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Determination of synergy by two methods with eight antimicrobial combinations against tobramycin-susceptible and tobramycin-resistant strains of pseudomonas

Cited by 38 publications

References 11 publications

Antibiotic combinations: should they be tested?

Antibiotic combinations: should they be tested?

Synergistic interactions of ciprofloxacin and extended-spectrum beta-lactams or aminoglycosides against multiply drug-resistant Pseudomonas maltophilia

Fractional Maximal Effect Method for In Vitro Synergy between Amoxicillin and Ceftriaxone and between Vancomycin and Ceftriaxone against Enterococcus faecalis and Penicillin-Resistant Streptococcus pneumoniae

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